The goal of this proposal is to develop a THz imaging system to image and spatially map the hydration of the cornea. Corneal hydration is currently measured using ultrasound pachymetry and is derived from an empiric relationship between central corneal thickness and available hydration data. This proposal will use corneal spectroscopy and reflectance data to improve models of THz reflectivity from the cornea. These models will be evaluated using phantoms and in-vivo rabbit corneas. Preliminary data suggest that THz imaging can measure corneal hydration with 0.1% accuracy and a spatial resolution of 600 um. The simulations and phantom models, and animal studies will be used to evaluate the feasibility of the approach and verify the ability of corneal THz imaging to discern hydration changes characteristic of corneal diseases. One of the advantages of THz radiation is its extremely low photon energy. It is eye safe and operates at 10 - 20 uW. To ensure safety for human use we will evaluate THz illumination on the cornea of rabbits at 50 5W and examine the corneas with histology and proteomic analysis. Once we have confirmed safety and obtained necessary IRB approvals we will conduct initial human corneal imaging trials in normal volunteers. After obtaining baseline information from normal patients (N = 60) we will proceed to study hydration in patients before and after DSEK surgery (N = 20), and before and after LASIK surgery (N = 20). Data accumulated from these studies will be analyzed to assess the feasibility of THz imaging to monitor hydration levels as a function of disease state. 1 PUBLIC HEALTH RELEVANCE: This project will develop a new imaging tool for non-contact, high resolution measurements of corneal hydration. This technology, THz imaging, is a low energy, safe imaging modality that has significant potential advantages over current measurement systems. This proposal develops the mathematical models, animal studies, and preliminary human feasibility testing to evaluate the potential of this new technology to detect, diagnose, and track hydration changes in the cornea as a function of disease. 2